KIF24

KIF24 is a microtubule-depolymerizing kinesin that acts at the mother centriole to suppress ciliogenesis in cycling cells (PMID:21620453). It binds and depolymerizes microtubules in vitro and selectively remodels centriolar microtubules, physically associating with the CP110 and Cep97 centriolar cap proteins, whose retention at the mother centriole depends on KIF24 (PMID:21620453). KIF24 functions as the upstream recruiter of MPP9 to the distal mother centriole, where MPP9 forms a ring-like structure and directly binds CEP97 to retain the CP110-CEP97 complex (PMID:30375385). Its microtubule-depolymerizing activity is switched on by NEK2-mediated phosphorylation during S/G2 phase, tilting the balance toward cilium disassembly independently of Aurora A and HDAC6 (PMID:26290419). Beyond ciliogenesis, KIF24 has a cilia-independent role in restraining centrosome clustering: in pancreatic ductal adenocarcinoma cells with supernumerary centrosomes, its depletion induces centrosome clustering, suppresses multipolar spindle formation, and promotes proliferation without recapitulation by cilia disruption (PMID:35803737).

1. 2011 High

   Established that KIF24 is a centriole-localized microtubule depolymerase that suppresses ciliogenesis, answering how the CP110-Cep97 cap restrains cilium formation through an enzymatic effector.

   Evidence Co-IP, in vitro microtubule depolymerization assay, immunofluorescence, and siRNA knockdown with ciliogenesis readout

   PMID:21620453

   Open questions at the time

   • Structural basis of selective centriolar versus cytoplasmic microtubule remodeling not defined
   • Mechanism of preferential mother-centriole targeting not resolved
2. 2015 High

   Identified NEK2 phosphorylation as the cell-cycle switch that activates KIF24, explaining how depolymerase activity is timed to S/G2 to keep proliferating cells cilium-free.

   Evidence In vitro kinase assay, co-localization imaging, siRNA epistasis, and ciliogenesis assay

   PMID:26290419

   Open questions at the time

   • Phosphosites on KIF24 not mapped to function
   • How phosphorylation mechanistically stimulates depolymerization unresolved
3. 2018 High

   Placed KIF24 upstream of MPP9 in CP110-CEP97 retention, defining the recruitment hierarchy that positions the centriolar cap at the distal mother centriole.

   Evidence Reciprocal Co-IP, immunofluorescence, siRNA knockdown ciliogenesis phenotype, and in vivo mouse kidney model

   PMID:30375385

   Open questions at the time

   • Direct binding interface between KIF24 and MPP9 not mapped
   • How MPP9 ring assembly is geometrically organized unclear
4. 2022 Medium

   Revealed a cilia-independent function of KIF24 in preventing centrosome clustering, showing its loss promotes bipolar spindles and proliferation in cancer cells with extra centrosomes.

   Evidence siRNA knockdown, spindle formation and proliferation assays, and cilia-disruption epistasis in PDAC cells

   PMID:35803737

   Open questions at the time

   • No biochemical reconstitution of the clustering-suppression mechanism
   • Single lab, single cancer-cell context
   • Molecular effectors linking KIF24 to centrosome separation unidentified

• How KIF24's two functions — ciliogenesis suppression and centrosome-clustering restraint — are molecularly partitioned remains open.
• No structural model of KIF24
• Mechanistic basis of cilia-independent centrosome role undefined